J. CHEM. RESEARCH (S), 1999 295
CuCl2 ÁH2O in Me2CO H2O (95:5 v/v) for 6 h gave the
Table
2
Deprotection of cyclic dioxolanes with
a
catalytic
amount of CuCl2 Á H2Oa
parent alcohol in only 25% isolated yield.
Reaction
timea/h
Isolated
Entry
Compound
5% mol CuCl2•H2O
ROH
yield (%)
90b
R
R
95% EtOH, reflux
2.0–3.0 h
O
O
O
O
1
3.0
2.5
2% mol CuCl2•H2O
O
ROH
Me2CO–H2O(95:5, v/v)
reflux, 1.0 h
O
OAc
94b
Scheme 1
2
O
O
H
In order to gain some insight into the mechanism of this
novel deprotection process, we investigated the reaction with
anhydrous CuCl2 in anhydrous EtOH. We found that both
THP and EE groups could be removed as e¤ciently as when
using CuCl2 Á2H2O in H2O-containing EtOH. Therefore,
H2O is not indispensable for these reactions. However,
re£uxing of EE protected compound with anhydrous
CuCl2 in anhydrous acetone led to decomposition to several
unidenti¢ed products. Additionally THF H2O (95:5 v/v)
was an unsuitable solvent for deprotection and led to no
reaction after re£uxing for several hours. We also tested
CuSO4 Á5H2O and Cu(acac)2 and found them to be ine¡ective
in the deprotection of THP or EE groups under the same
conditions.
Since an aqueous solution of CuCl2 is acidic (pH 3.6 in
0.2 M aqueous solution), it is most possible that these
deprotection reactions are simply acid-catalyzed hydrolysis
of acetals. However, considering the catalytic amount of
CuCl2 in the reaction system, it is also likely that metal
complexation is involved in the reaction so as to facilitate.
Sen et al. recently reported that FeCl3 Á 6H2O could remove
THP protecting groups.5 It seems likely that these processes
have some common feature in the reaction pathway. However,
the detailed mechanism for CuCl2-promoted deprotection is
still unclear.
In Table 1 (entry 5), both THP and dioxolane groups in the
3b-OH and 17-oxo-protected epiandrosterone were found to
be removed under the CuCl2-promoted deprotection con-
ditions. This suggests that dioxolane groups in general might
be also removed under the same reaction conditions. We then
investigated the ability of CuCl2 Á2H2O to cleave cyclic
dioxolane derivatives. Thus, ketals and acetals were prepared
according to standard procedures,1 and the deprotection
was conducted under the same conditions as for the THP
ethers and results are summarized in Table 2. Although
the deprotection indeed worked in most of cases, the reaction
generally takes longer than for corresponding deprotection of
THP or EE groups. In several cases, the reaction did not
proceed to completion (Table 2, entries 3, 4 and 5). In
one case, the acetal group was not cleaved and the starting
material was recovered unchanged (entry 6).
O
3
4
5.5
7.5
95(5)c
O
O
47(53)c
Me(CH2)20
C
O
H
O
O
90(10)c
0(100)c
5
6
4.5
3.5
O
O2N
O
a Reaction conditions: CuCl2 ÁH2O was refluxed with the protected
compound in 95% EtOH. b 5% mol CuCl2 ÁH2O was used. The
deprotections were complete, and the yields refer to isolated yield.
c 10% mol CuCl2 ÁH2O was used. The reactions were not complete.
The relative yields were estimated by 1H NMR and the numbers in
parentheses refer to unreacted materials.
CuCl2 ÁH2O (0.05 or 0.01mmol and the homogenous solution was
heated under gentle re£ux until completion of the reaction
(monitored by TLC). After cooling, the solvent was removed by
evaporation. Diethyl ether (30 mL) was added to the residue, and
the mixture was washed with H2O and saturated aqueaus NaCl.
The ethereal solution was dried over anhydrous MgSO4. Removal
of the drying agent and the solvent gave a crude product, which
was puri¢ed by column chromatography with silica gel. The pure
parent compound was identi¢ed by comparison with an authentic
sample (TLC, 1H NMR, 13C NMR).
Financial support by the State Education Commission of
China (Excellent Young Teacher's Foundation to J. W.),
and NSFC (Grant No. 29702002) is gratefully acknowledged.
Received, 8th January 1998; Accepted, 20th January 1999
Paper E/9/00262F
Reference
1
T. W. Greene and P. G. M. Wutz, Protective Groups in Organic
Synthesis, John Wiley and Sons, Inc., New York, 1991.
ꢀa I. Mohammadpoor-Baltork and S. Pouranshirvani,
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Viswajananii and C. V. Yelamaggad, J. Org. Chem., 1995,
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Mioskowski, J. Chem. Soc., Chem. Commun., 1989, 1619;
ꢀ f S. Kim and J. H. Park, Tetrahedron Lett., 1987, 28, 439;
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However, we found that tert-butyldimethylsilyl(TBDMS) ethers
were also hydrolyzed under these conditions.
S. G. Sen, S. L. Roach, J. K. Boggs, G. J. Ewing and J.
Magrath, J. Org. Chem., 1997, 62, 6684.
In conclusion, we have discovered an e¤cient method for
the deprotection of THP and EE groups. The reaction is
remarkably simple and requires only a catalytic amount of
inexpensive and readily available copper(II) chloride
dihydrate.
2
Experimental
CuCl2 Á2H2O was obtained from Beijing Chemical Reagent Co.,
China and anhydrous CuCl2 was purchased from Aldrich. All solvents
were distilled prior to use. 100^200 Mesh silica gel (Qingdao, China)
was employed for column chromatography puri¢cation. THP ethers,
EE ethers and dioxolane derivatives were prepared by standard pro-
cedures and characterized by 1H (200 MHz) and 13C NMR (50 MHz).
General Procedure for Deprotection with CuCl2 ÁH2O.öThe
protected compound (1mmol) was dissolved in 95% EtOH (10 mL)
or Me2CO H2O (95:5 v/v; 10 mL). To the solution was added
3
4
5
Wang, Jianbo
